We are studying alpha virus vectors expressing retroviral proteins as potential vaccines. Alpha virus vectors replicate their RNA extensively, leading to increased levels of expression of vector-encoded proteins. We made Sindbis and Semliki Forest virus vectors encoding various forms of murine leukemia virus envelope proteins and achieved high levels of expression of envelope protein on the cell surface. When such cells were disrupted by dounce homogenization, they formed small vesicles containing envelope protein on the surface and vector RNA inside. These vesicles were able to fuse with cells bearing the murine leukemia virus receptor, leading to a second round of vector replication and envelope expression. Mice inoculated intramuscularly with such vesicles expressed vector-encoded protein in muscle. We found that we could switch the roles of envelope and receptor in this system by constructing vectors that encoded the murine leukemia virus receptor instead of envelope. Vesicles derived from cells electroporated with such vectors transferred vector RNA specifically to cells bearing an activated form of envelope on their surface. Such "reverse vesicles" might be useful to target alpha virus vectors to kill retrovirus-infected cells.